In practice, the measurement of the glucose concentration is usually done indirectly through an enzymatic conversion of the glucose with subsequent detection of the hydrogen peroxide released during the conversion reaction, being proportional to the glucose concentration, or the oxygen consumed, for example, by a color change reaction, a fluorescence measurement, or an electrochemical determination. For this, a blood sample is first placed on a test strip, for example. The drawback to this measurement based on enzymatic conversion of glucose is that it can only be performed discontinuously and therefore needs to be repeated often, and the test strip can only be used once. There is also a quasi-continuous measurement by means of an implanted, enzymatically functionalized sensor surface, based on enzymatic conversion of glucose. But the lifetime of such a sensor is limited by the progressive consumption of the enzyme. Furthermore, the consumption of the enzyme requires a readjusting or calibrating of the sensor at regular intervals (several times a day). Finally, the precision of the best sensors of this type in the relevant measurement range is around 50 to 250 mg/dl with a mean absolute error (MARE) of less than 10%.
DE 10 2009 010 955 A1 specifies a method and a measurement device for the determination of blood sugar values in the form of the glucose or fructose determination in human blood by means of optical spectroscopy. It is proposed to implant an optical, monolithic, miniaturized spectrometer in the human body, having a measurement cell in the form of a measurement fiber, which is introduced by its fiber end directly into the blood stream of a person. The measurement fiber has a recess at its distal end, constantly washed by blood, and a coupling site at its opposite proximal end, which is connected to a light-conducting disk. The light-conducting disk forms a unit with a silicon disk, on which is arranged an evaluating unit. The evaluating unit evaluates the measurement data, stores it or transmits it by telemetry to an insulin pump or a heart rate monitor for display. This arrangement records a remitted absorption spectrum of the scattered light in the blood stream of the person, from which the blood sugar value and/or other blood values are determined. The drawback to this method and measurement device is, in particular, that the recess in the measurement fiber forms a predetermined breaking point and increases the risk of the end of the measurement fiber breaking off during improper handling or careless movement of the patient, getting into the blood stream, and endangering the patient. Another drawback is that the absorption measurement in the blood can be influenced by other effects, such as a buildup of blood cells in the area of the recess, which would impair the glucose detection accuracy. Document US 2009/0088615 A1 teaches the same measurement principle.
Furthermore, there have been studies with the participation of the inventor on glucose determination by measurement of differential absorbance in the near infrared spectrum, as described for example in the article “A minimally invasive chip based near infrared sensor for continuous glucose monitoring”, L. Ben Mohamadi et al, Proc. of SPIE Vol. 8427 84270K-1. In this method, a perfusion solution is pumped by means of a dialysis pump through a subcutaneously or intravenously applied dialysis needle (catheter), across a semipermeable membrane (typically with a separation capacity of 20 kDa), which is not permeable to blood cells and larger fat or protein molecules, but is so for the perfusate and the glucose, the glucose diffusing from the blood or interstitial fluid into the perfusate. The specimen (analyte) so obtained is transported into a microfluidic chip with infrared light source and a photosensitive detector (GaAs photodiode), where a change in the NIR absorption dependent on the glucose concentration is compared against a reference measurement at a reference cell filled with pure liquid. This so-called absorption difference measurement provides a measurement precision with a mean absolute relative error (MARE) of around 5%. The drawback to this measurement method, among other things, is the large distance between the sampling point of the analyte, i.e., the dialysis needle on the one hand, and the detection cell on the other hand, in conjunction with a low flow rate of the perfusate/analyte, which is required for an adequate buildup of glucose in the perfusate. This typically causes a time delay from the sampling to the evaluation of around 10 minutes. Moreover, a considerable expense is necessary in order to operate the measurement cell and the reference cell under the same external, especially thermal, conditions, so that any differences will not negatively affect the measurement result. Document DE 20 2007 019 544 U1 teaches the same measurement principle.